Up-Regulation of Glutamate Receptors in Nucleus Tractus Solitarii Underlies Potentiation of Baroreceptor Reflex by Heat Shock Protein 70

Chan, Samuel H.H.; Chang, Kui-Fen; Ou, Chen-Chun; Chan, Julie Y.H.

doi:10.1124/mol.61.5.1097

Cited by 19 publications

(24 citation statements)

References 42 publications

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“…15 Heightened expression of HSP70 was reported in vascular smooth muscle cells of SHR. 13,20 The present study, however, revealed that instead of quantity, it is the kinetics of HSP70 induction by HS in the dorsomedial medulla that is crucial to the altered heat stress response in SHR.…”

Section: Discussionmentioning

confidence: 99%

“…3,15,16 Primary antisera used included mouse monoclonal antiserum against the inducible form of HSP70 (1:500; SPA-810, StressGen) or rat monoclonal antiserum against HSF1 (1:500, MAB88078; Chemicon) or HSF2 (1:500, MAB88079; Chemicon).…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

“…Microinjection bilaterally into the NTS of test agents was carried out 3,15 immediately after HS. The coordinates were Ϫ0.5 to ϩ0.5 mm from obex, 0.3 to 0.8 mm lateral to midline, and 0.5 to 1.0 mm below dorsal surface of the medulla oblongata.…”

Section: Microinjection Of Test Agents Into the Ntsmentioning

confidence: 99%

“…Hyperthermic HS was induced by maintaining the core temperature of animals at 42Ϯ0.5°C for 15 minutes, 3,15 as monitored by a thermistor probe placed in the colon. Animals were thereafter allowed to recover at room temperature for the time interval stipulated for each experiment.…”

Section: Hs Inductionmentioning

confidence: 99%

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Altered Temporal Profile of Heat Shock Factor 1 Phosphorylation and Heat Shock Protein 70 Expression Induced by Heat Shock in Nucleus Tractus Solitarii of Spontaneously Hypertensive Rats

et al. 2003

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Background-We demonstrated recently that heat shock (HS)-induced heat shock protein 70 (HSP70) expression in bilateral nucleus tractus solitarii (NTS), the terminal site in the brain stem for primary baroreceptor afferents, confers cardiovascular protection against heatstroke by potentiating baroreceptor reflex (BRR) response. This study evaluated the hypothesis that altered regulation of HSP70 expression may be associated with the heightened susceptibility to heatstroke during hypertension. Methods and Results-Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats anesthetized with propofol were used. Compared with WKY rats, significant induction in HSP70 or phosphorylation of heat shock factor 1 (HSF1), but not HSF2, in the NTS and potentiation of BRR response in SHR occurred earlier (4 versus 8 hours), reaching peak magnitude sooner (16 versus 24 hours), and declined more rapidly after a brief hyperthermic HS (42Ϯ0.5°C for 15 minutes). The protection conferred by HS against hypotension and bradycardia during the onset of heatstroke (45°C for 60 minutes), although effective, was less effective in SHR. Microinjection bilaterally into the NTS of the selective protein kinase A (PKA) inhibitor H-89 (100 pmol) or the selective PKC inhibitor calphostin C (100 pmol) significantly attenuated all of the above events induced in SHR by HS. However, only H-89 was effective in WKY rats. Conclusions-An

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Section: Discussionmentioning

confidence: 99%

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

Section: Microinjection Of Test Agents Into the Ntsmentioning

confidence: 99%

Section: Hs Inductionmentioning

confidence: 99%

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Altered Temporal Profile of Heat Shock Factor 1 Phosphorylation and Heat Shock Protein 70 Expression Induced by Heat Shock in Nucleus Tractus Solitarii of Spontaneously Hypertensive Rats

et al. 2003

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“…27,28 This was followed by incubation with horseradish peroxidase-conjugated goat anti-rabbit IgG (Jackson). Specific antibody-antigen complex was detected with the use of an enhanced chemiluminescence Western blot detection system (NEN Life Science Products).…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

Downregulation of Angiotensin Subtype 1 Receptor in Rostral Ventrolateral Medulla During Endotoxemia

Chan

Ling-lin

et al. 2003

Hypertension

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Abstract-We reported recently that an upregulation of the inducible nitric oxide synthase (iNOS) in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons are located, is a crucial determinant for the elicitation of cardiovascular depression during experimental endotoxemia. The current study evaluated the hypothesis that a downregulation of the molecular synthesis and functional expression of angiotensin subtype 1 receptor (AT1R) in the RVLM is consequential to this upregulated iNOS. In adult Sprague-Dawley rats maintained under propofol anesthesia, intravenous administration of Escherichia coli lipopolysaccharide (15 mg/kg) elicited a reduction, followed by an augmentation and a secondary decrease in sympathetic vasomotor outflow, together with progressive hypotension and bradycardia. There was also a progressive increase in iNOS mRNA and protein level in the ventrolateral medulla. This was followed by a significant downregulation of both mRNA and protein levels of AT1R in the ventrolateral medulla, alongside reduced efficacy of angiotensin II (50 pmol) to induce an increase in systemic arterial pressure, heart rate, or sympathetic vasomotor outflow on unilateral microinjection into the RVLM. Pretreatment with microinjection of a selective iNOS inhibitor, S-methylisothiourea (250 pmol) bilaterally into the RVLM significantly reversed the reduction in both synthesis and activity of AT1R. We conclude that a downregulation of molecular synthesis and functional expression of AT1R in the ventrolateral medulla is consequential to the overproduction of NO through upregulation of iNOS in the RVLM and may underlie the cardiovascular depression that takes place during experimental endotoxemia. Key Words: receptors, angiotensin Ⅲ nitric oxide synthase Ⅲ central nervous system Ⅲ hypotension Ⅲ bradycardia Ⅲ nervous system, sympathetic S epsis is associated with profound cardiovascular abnormalities characterized by hypotension, decreased systemic resistance, altered vascular reactivity to contractile agents, and a high mortality rate. 1 One well-known mediator of sepsis-induced circulatory failure is nitric oxide (NO) produced through activation of the inducible NO synthase (iNOS) in macrophages at the peripheral vasculature. 2,3 In addition, we reported recently 4 that overproduction of NO by iNOS in the rostral ventrolateral medulla (RVLM) is also a crucial determinant for the reduction in sympathetic vasomotor outflow and fatal cardiovascular depression during experimental endotoxemia. Whereas we proposed that the underlying mechanisms include formation of the cytotoxic substance peroxynitrite 5 and activation of GABAergic neurotransmission, 6 the possibility exists for the engagement of other mediators in the RVLM.As the medullary site of the sympathetic premotor neurons, 7 the RVLM maintains arterial pressure by providing a tonic excitation to preganglionic sympathetic neurons in the spinal cord. 7,8 It is also a target site where the brain renin-angiotensin system acts to regulate sympathetic out...

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AMPA, kainate, and NMDA receptor densities in the hippocampus of untreated male rats and females in estrus and diestrus

Palomero‐Gallagher

Bidmon²,

Zilles

2003

J of Comparative Neurology

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Steroid hormones systematically affect numerous neuronal targets, thus influencing, in a permanent or a transitory manner, the way the brain reacts to external and internal stimuli. The hippocampus is an important brain region for learning and memory and the glutamatergic intrahippocampal pathway plays a major role in performing such functions. We applied quantitative in vitro receptor autoradiography to examine how the in vivo hormone milieu affects the densities of AMPA, kainate, and NMDA receptors in the hippocampus of adult male rats and females in estrus and diestrus. All three examined receptor types presented significant gender-specific differences in their densities. The hippocampus of male rats contains significantly more AMPA, kainate, and NMDA receptors than that of female rats. Female rats in diestrus have significantly higher AMPA receptor densities than female rats in estrus. AMPA changes occurred to the same extent in CA1-3 and in the dentate gyrus. Significant differences in the densities of NMDA receptors were observed in the CA1-3 regions, whereas kainate receptor differences were restricted to the CA1 region. These results further support that steroid hormones, through their modulation of AMPA and NMDA receptors, may be involved in the control of synaptic efficacy and, therefore, influence learning and memory.

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Up-Regulation of Glutamate Receptors in Nucleus Tractus Solitarii Underlies Potentiation of Baroreceptor Reflex by Heat Shock Protein 70

Cited by 19 publications

References 42 publications

Altered Temporal Profile of Heat Shock Factor 1 Phosphorylation and Heat Shock Protein 70 Expression Induced by Heat Shock in Nucleus Tractus Solitarii of Spontaneously Hypertensive Rats

Altered Temporal Profile of Heat Shock Factor 1 Phosphorylation and Heat Shock Protein 70 Expression Induced by Heat Shock in Nucleus Tractus Solitarii of Spontaneously Hypertensive Rats

Downregulation of Angiotensin Subtype 1 Receptor in Rostral Ventrolateral Medulla During Endotoxemia

AMPA, kainate, and NMDA receptor densities in the hippocampus of untreated male rats and females in estrus and diestrus

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